2020美國癌症研究協會演講: Informatics Technologies for Cancer Research

這個演講系列由聖路易斯華盛頓大學的Obi L. Griffith教授做主席來規劃,有四個子演講組成,線上演講的連結在此。腫瘤研究者該如何面對巨量高通量的定序資料呢?本演講主要在談論有甚麼資訊處理工具可以用來幫助臨床上對於這些資料的管理、分析、視覺化和判讀,另外,也會介紹一些基本的觀念、標準、指引。最後,也會分享在臨床判讀腫瘤圖片和腫瘤影像在生物標誌發展的方式。除了Obi Griffith教授,還有約翰霍普金斯的計算機學家Rachel Karchin哈佛大學放射學教授Andrey Fedorov華盛頓聖路易斯大學Daniel Marcus

將定序資料導入臨床腫瘤科使用,最大的障礙就是如何去解讀變異,或是去判斷哪個變異是有臨床意義的,到現在這始終是個"百萬美元"的問題,下面這張圖便是來自於Griffith教授在2014年的文章:Organizing knowledge to enable personalization of medicine in cancer,裡面談論到他覺得可能的解法,便是建立一個開源群眾註解和判讀的知識庫。

Good BM, Ainscough BJ, McMichael JF, Su AI, Griffith OL. Organizing knowledge to enable personalization of medicine in cancer. Genome Biol. 2014;15(8):438. Published 2014 Aug 27. doi:10.1186/s13059-014-0438-7

Standardized and genome-wide clinical interpretation of complex genotypes for cancer precision medicine

第一個演講便是Obi L. Griffith教授介紹其發展的線上資料庫CIViC,也算是他2014年提出的概念的實踐版本,一個可以用來做腫瘤變異判讀的知識庫,其終極目地為用來做腫瘤精準治療所使用,其代碼開源且提供API串接,且期望建立一套良好的註解規則讓不同層級的人可以為其做貢獻。

CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer. 2017. Nature Genetics

Informatics tools for high-throughput analysis of cancer mutations

第二個部分是由約翰霍普金斯的計算機學家Rachel Karchin發展的工具Open CRAVAT,相對於前一部分想要使用專家和社群的方式來解決基因變異註解的問題,這個工具相對於CIVIC,比較著重在串接各種資料庫和用計算生物學的方法給予變異一些排序和解釋。

Integrated Informatics Analysis of Cancer-Related Variants. 2020. JCO Clin Cancer Inform

這個系列也分享了一些目前基因資訊處理和共享的指引,主要是由美國醫學遺傳學暨基因體學學會(ACMG)提到的

Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. 2015

Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer. 2017

Standard operating procedure for curation and clinical interpretation of variants in cancer. 2019

The FAIR Guiding Principles for scientific data management and stewardship. 2016

科學寫作:Writing in the Science (一)

這一系列主要有鑒於最近發現我的寫作能力實在是有很多提升空間,所以想再鍛鍊寫作肌肉,這系列主要來自於Coursera: Writing in the Science 的上課心得和筆記。

起手式當然是重新加強一下觀念,重溫一些原則,如何往一個更好的寫手邁進:

  • 閱讀、刻意去關注文章是如何寫的、並且模仿看看
  • 每日或是定期的寫作
  • 請拋棄堆砌文字的壞習慣
  • 先談談(找好朋友喝咖啡的意思)你做的研究,再下手來撰寫
  • 不要等待靈感再來寫作
  • 接受寫作對於任何人來說都是很困難的
  • 不段重寫,沒有人第一次就能寫好,大多數人留太少時間再重寫,都想一次到位

聽完這些,就一定要列一下自己目前看過很會寫作的作者,當作觀摩目標,下面這些是我自己回億起來,閱讀他們的文字很令人愉悅和開心,有點會上癮的那種滋味!

  • John M.Chamber
  • Hadley Wickham
  • Jales J. Berman
  • Stephan Wolfram
  • Uri Alon
  • Bernhard Palsson
  • Leroy Hood
  • Bradley Efron
  • Trevor Hastie
  • Tim O’Reily

收集幾本跟寫作相關的好書:

這邊有幾個範例,來體會一下如何把字句更加地讓人易理解,下面是一個節錄自The Journal of Clinical Oncology的開頭:

Adoptive cell transfer (ACT) immunotherapy is based on the ex vivo selection of tumor-reactive lymphocytes, and their activation and numerical expression before reinfusion to the autologous tumor-bearing host

仔細思考上面這個段落,會發現一個學術論文很喜愛的模式,過度使用“名詞”(clunky nouns),假如要讓字串更簡單俐落,就必須要減少這類使用,以“動詞”主導論述。

These findings imply that the rates of ascorbate radical production and its recycling via dehydroascorbate reductase to replenish the ascorbate pool are equivalent at the lower irradiance, but not equivalent at higher irradiance with the rate of ascorbate radical production exceeding its recycling back to ascorbate"

修改過後如下,整體的可讀性增加,更容易理解且順暢。

These findings imply that, at low irradiation, ascorbate radicals are produced and recycled at the same rate, but at high irradiation, they are produced faster than they can be recycled back to ascorbate

如何寫的簡白(Effective Writing)的三個要點

  • 減少不必要且意義模糊的用字原則(Cut the clutter)
  • 主動語氣
  • 使用洽當的動詞

盡可能減少多餘的字,你永遠都會驚訝於能使用更少的字來表達同樣的道理

範例一

This paper provides a review of the basic tenets of cancer biology study design, using as examples studies that illustrate the methodologic challenges or that demonstrate successful solutions to the difficulties inherent in biology result.

This paper provides a review of the basic tenets of cancer biology study design, using as examples studies that illustrate the methodologic challenges or that demonstrate successful solutions to the difficulties inherent in biology result. [高手改]

範例二

As it is well known, increased athletic activity has been related to a profile of lower cardiovascular risk, lower blood pressure levels, and improved muscular and cardio-respiratory performance

Increased athletic activity is known to lower cardiovascular risk and pressure levels, and improved muscular and cardio-respiratory performance[土炮練習]

Increased athletic activity is associated with lower cardiovascular risk, lower blood pressure, and improved fitness. [高手改的]

範例三

The experimental demonstration is the first of its kind and is a proof of principle for the concept of laser driven particle acceleration in a structure loaded vacuum

The experiments demonstrate the proof of concept that laser-driven particle can accelerate in the structure loaded vacuum. [土炮練習]

The experiment provides the first of principle of laser-driven particle acceleration in a structure-loaded vacuum.[高手改]

範例四

Brain injury incidence shows two peak periods in almost all reports: rates are the highest in young people and the elderly

Brain injury incidence peaks in young and the elderly [高手改]